N-Methylserotonin hydrogen oxalate

The structure of the natural product N-methylserotonin is reported as its hydrogen oxalate salt.

data reports serotonin has been observed both in plants and mammals, including in rodents colonized with human gut bacterial strains (Han et al., 2022). The biosynthesis of N-methylserotonin most likely occurs via N-methylation of serotonin by the enzyme indolethylamine-N-methyltransferase (Thompson et al., 2001). This enzyme, originally discovered as the enzyme responsible for the synthesis of the endogenous hallucinogen dimethyltryptamine (Barker et al., 2012), has recently been shown to have a broader substrate scope, including serotonin, which likely leads to the formation of N-methylserotonin (Chu et al., 2014).
The pharmacological properties of N-methylserotonin have been a subject of increasing interest. It is reported to have significant binding affinity for the serotonin 1 A and 7 receptors, in addition to being a potent serotonin reuptake inhibitor (Powell et al., 2008). These activities suggest that N-methylserotonin may have a unique pharmacological profile different from parent serotonin and may provide novel therapeutic opportunities for various psychiatric and neurological disorders. The title compound was first synthesized by Hofmann in 1955 and characterized by IR and elemental analysis (Stoll et al., 1955). Herein, the crystal structure of 5-hydroxy-Nmethyltryptamine is presented as its hydrogen oxalate salt.
The asymmetric unit of 5-hydroxy-N-methyltryptammonium hydrogen oxalate contains one tryptammonium cation and one hydrogen oxalate anion (Fig. 1). The tryptammonium cation has a near planar indole unit with an r.m.s. deviation from planarity of 0.014 Å . The ethylamino arm is turned away from the indole plane with a C7-C8-C9-C10 torsion angle of À83.1 (3) . The N-methyl group of this arm possesses a gauche configuration , with a C9-C10-N2-C11 torsion angle of 57.2 (3) . The hydrogen oxalate anion varies significantly from planarity, with a CO 2 -to-CO 2 plane-to-plane twist angle of 24.2 (1) . The ions are linked together through a series of N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds into a three-dimensional framework (Fig. 2, Table 1). The hydrogen oxalate ions are linked together through O-HÁ Á ÁO hydrogen bonds into chains along (100).

Figure 2
The crystal packing of 5-hydroxy-N-methyltryptammonium hydrogen oxalate shown along the a-axis. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding are omitted for clarity. Table 1 Hydrogen-bond geometry (Å , ).

Figure 1
The molecular structure of 5-hydroxy-N-methyltryptammonium hydrogen oxalate showing the atomic labeling. Displacement ellipsoids are drawn at the 50% probability level. Hydrogen bonds are shown as dashed lines.

Synthesis and crystallization
Single crystals suitable for X-ray diffraction studies were grown from an aqueous solution of a commercial sample (Sigma-Aldrich).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2.

Acknowledgements
Financial statements and conflict of interest: This study was funded by CaaMTech, Inc. ARC reports an ownership interest in CaaMTech, Inc., which owns US and worldwide patent applications, covering new tryptamine compounds, compositions, formulations, novel crystalline forms, and methods of making and using the same.

Funding information
Funding for this research was provided by: National Science Foundation (grant No. CHE-1429086).  Special details Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.